17-35548292-A-G

Variant names:

• chr17-35548292-A-G
• rs2072550081
• NM_001129820.2:c.2686T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001129820.2(SLFN14):​c.2686T>C​(p.Ser896Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLFN14 NM_001129820.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.63
• Publications: 0 publications found

Genes affected

SLFN14 (HGNC:32689): (schlafen family member 14) The protein encoded by this gene plays an important role in platelet formation and function. Defects in this gene are a cause of thrombocytopenia with excessive bleeding. [provided by RefSeq, Jul 2016]

SLFN14 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 20

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001129820.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN14	NM_001129820.2	MANE Select	c.2686T>C	p.Ser896Pro	missense	Exon 6 of 6	NP_001123292.1	P0C7P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLFN14	ENST00000674182.1	MANE Select	c.2686T>C	p.Ser896Pro	missense	Exon 6 of 6	ENSP00000501524.1	P0C7P3-1
	SLFN14	ENST00000415846.3	TSL:1	c.2686T>C	p.Ser896Pro	missense	Exon 4 of 4	ENSP00000391101.2	P0C7P3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Thrombocytopenia;C1458140:Abnormal bleeding (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.083	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.6
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.76
MutPred		0.56		Loss of helix (P = 0.079)
MVP		0.58
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2072550081; hg19: chr17-33875311;